TY - JOUR
T1 - Antithrombin inhibits bronchoalveolar activation of coagulation and limits lung injury during Streptococcus pneumoniae pneumonia in rats
AU - Choi, Goda
AU - Hofstra, Jorrit-Jan H.
AU - Roelofs, Joris J. T. H.
AU - Rijneveld, Anita W.
AU - Bresser, Paul
AU - van der Zee, Jaring S.
AU - Florquin, Sandrine
AU - van der Poll, Tom
AU - Levi, Marcel
AU - Schultz, Marcus J.
PY - 2008
Y1 - 2008
N2 - Objective: Alveolar fibrin deposition is a hallmark of pneumonia. It has been proposed that natural inhibitors of coagulation, including activated protein C, antithrombin, and tissue factor pathway inhibitor, exert lung-protective effects via anticoagulant and possibly anti-inflammatory pathways. We investigated the role of these natural anticoagulants in Streptococcus pneumoniae pneumonia. Design: A controlled in vivo laboratory.study. Setting. Research laboratory of a university hospital. Subjects. Total of 98 male Sprague-Dawley rats. Interventions. Rats were challenged intratracheally with S. pneumoniae (serotype 3, 106 colony forming units), inducing pneumonia. Rats were randomized to intravenous treatment with normal saline, activated protein C, antithrombin, tissue factor pathway inhibitor, heparin, or tissue-type plasminogen activator. Measurements and Main Results: Rats infected with S. pneumoniae had increased thrombin-antithrombin complexes in bronchoalveolar lavage fluid, with decreased levels of antithrombin activity and fibrin degradation products. Administration of activated protein C, antithrombin, and tissue factor pathway inhibitor significantly limited these procoagulant changes. Furthermore, antithrombin treatment resulted in less bacterial outgrowth of S. pneumoniae and less histopathologic damage in lungs. Conclusions. Anticoagulant treatment attenuates pulmonary coagulopathy during S. pneumoniae pneumonia. Antithrombin seems to exert significant lung-protective effects in pneumococcal pneumonia in rats
AB - Objective: Alveolar fibrin deposition is a hallmark of pneumonia. It has been proposed that natural inhibitors of coagulation, including activated protein C, antithrombin, and tissue factor pathway inhibitor, exert lung-protective effects via anticoagulant and possibly anti-inflammatory pathways. We investigated the role of these natural anticoagulants in Streptococcus pneumoniae pneumonia. Design: A controlled in vivo laboratory.study. Setting. Research laboratory of a university hospital. Subjects. Total of 98 male Sprague-Dawley rats. Interventions. Rats were challenged intratracheally with S. pneumoniae (serotype 3, 106 colony forming units), inducing pneumonia. Rats were randomized to intravenous treatment with normal saline, activated protein C, antithrombin, tissue factor pathway inhibitor, heparin, or tissue-type plasminogen activator. Measurements and Main Results: Rats infected with S. pneumoniae had increased thrombin-antithrombin complexes in bronchoalveolar lavage fluid, with decreased levels of antithrombin activity and fibrin degradation products. Administration of activated protein C, antithrombin, and tissue factor pathway inhibitor significantly limited these procoagulant changes. Furthermore, antithrombin treatment resulted in less bacterial outgrowth of S. pneumoniae and less histopathologic damage in lungs. Conclusions. Anticoagulant treatment attenuates pulmonary coagulopathy during S. pneumoniae pneumonia. Antithrombin seems to exert significant lung-protective effects in pneumococcal pneumonia in rats
U2 - https://doi.org/10.1097/01.CCM.0000292012.87482.F4
DO - https://doi.org/10.1097/01.CCM.0000292012.87482.F4
M3 - Article
C2 - 18090375
SN - 0090-3493
VL - 36
SP - 204
EP - 210
JO - Critical Care Medicine
JF - Critical Care Medicine
IS - 1
ER -